Cartilage-Hair Hypoplasia

Cartilage-hair hypoplasia is a disease affecting the bone metaphyses causing small stature from birth.

Epidemiology

Prevalence is unknown.

Clinical description

The disease is associated with fine, slow growing hair, and sometimes with immune deficiencies. Other symptoms include short hands and possibly short, deformed limbs (varus). X-ray reveals metaphyseal lesions, especially in the knees, and large, round epiphyses during childhood. Short stature is common and has very early onset but immune deficiency is not always present. The disease course is variable.

Etiology

Mutations in the RMRP (RNA component of mitochondrial RNA-processing endoribonuclease) gene, which maps to the 9p21-p12 locus, are responsible for the disease.

Diagnostic methods

The diagnosis is confirmed by direct sequencing of the RMRP gene.

Differential diagnosis

The differential diagnosis should include other forms of short-limb dwarfism.

Antenatal diagnosis

A recurrence risk of 25% justifies prenatal diagnosis, which is possible through molecular analysis if the causative mutation has already been identified in a proband. Micromelia may be detected early in pregnancy during ultrasound follow up, but is not specific.

Genetic counseling

Cartilage-hair hypoplasia is inherited in an autosomal recessive manner.

Management and treatment

Immunodeficiency, when severe, may require bone marrow transplantation but this does not have any effect on the growth deficiency.

Prognosis

The prognosis depends on the presence and severity of the immune deficiency and the possible association with Hirschsprung disease (see this term).